A Safety, Tolerability, Pharmacokinetic and Efficacy Study of Azithromycin Plus Piperaquine as Presumptive Treatment in Pregnant PNG Women

Papua New Guinea Institute of Medical Research150 enrolled

Overview

Plasmodium falciparum parasitaemia in pregnancy is associated with maternal anaemia, low birth-weight and increased perinatal mortality. Whilst continuous prophylaxis is difficult to implement, intermittent presumptive treatment in pregnancy (IPTp) has proved to be practical and effective. In PNG, pregnant women currently receive IPTp using sulfadoxine-pyrimethamine, however, this therapy has the potential to be compromised by parasite resistance. The aim of the present trial is to assess the safety, tolerability, pharmacokinetics and efficacy of azithromycin (AZI) plus piperaquine (PQ) given as IPTp to pregnant Papua New Guinea women. The study will comprise of two sub-studies: (i) A safety, tolerability and pharmacokinetic study of AZI-PQ in pregnancy. (ii) A safety, tolerability and preliminary efficacy study of AZI-PQ in pregnancy.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

150

Conditions

Pregnancy Infections, Plasmodia Drug Kinetics Clinical Efficacy

Eligibility

Sex: FEMALEMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * \>14 weeks and \<30 weeks gestation * No signs of severe malaria by World Health Organisation criteria * No significant concomitant disease (such as TB) * No prior history of an adverse reaction to AZI or PQP * No prior treatment with these drugs in the past 4 weeks * Can attend all follow-up visits * Provide informed consent Exclusion Criteria: * Have signs of severe malaria by WHO criteria * Significant concomitant disease such as TB as assessed by the attending clinician * A history/family history of sudden death or of congenital prolongation of the QTc interval * Any clinical condition known to prolong the QTc interval * A history of complicated pregnancies/deliveries * A prior history of an adverse reaction to AZI or PQP * Have taken these drugs in the past 4 weeks * Cannot attend any of the follow-up visits * Do not provide informed consent

Outcomes

Primary Outcomes

Efficacy of azithromycin plus piperaquine for the prevention of malaria during pregnancy

The efficacy of azithromycin plus piperaquine for the prevention of malaria infection during pregnancy will be investigated in 120 women. Women will be randomized to receive either (i) 3 daily doses of AZI plus PQ, or, (ii) single dose sulfadoxine-pyrimethamine Participants will be actively followed for a period of 42 days (1, 2, 3, 4, 7, 14, 21, 28 and 42 days after treatment). At each follow-up time point the participant will have a clinical examination, fundal height measurement and assessment of foetal lie, perform a symptoms questionnaire, blood film for malaria and other scheduled safety tests (eg. Hb, glucose, ultrasound). A single blood sample for pharmacokinetic analysis will be collected at Day 4. At delivery all participants and their babies will be assessed, including blood sample for Hb, glucose, blood spot for PCR, cord blood and maternal blood. Breast milk samples will be collected for 2 weeks (Day 1, 2, 3, 4, 7, 14) after the establishment of lactation.